Nanoscale Structural\nCharacterization of Amyloid β\n1–42 Oligomers and Fibrils Grown in the Presence of Fatty Acids

Mono- and polyunsaturated fatty acids (FAs) are broadly\nused as\nfood supplements. However, their effect on the aggregation of amyloidogenic\nproteins remains unclear. In this study, we investigated the effect\nof a large number of mono- and polyunsaturated, as well as fully saturated\nFAs on the aggregation of amyloid β<sub>1–42</sub> (A<sub>β1–42</sub>) peptide. A progressive aggregation of this\npeptide is the expected molecular cause of Alzheimer’s disease\n(AD), one of the most common neurodegenerative pathologies in the\nworld. We found that arachidonic and stearic acids delayed the aggregation\nof Aβ1–42. Using Nano-Infrared spectroscopy, we found\nthat FAs caused very little if any changes in the secondary structure\nof A<sub>β1–42</sub> oligomers and fibrils formed at\ndifferent stages of protein aggregation. However, the analyzed mono-\nand polyunsaturated, as well as fully saturated FAs uniquely altered\nthe toxicity of Aβ1–42 fibrils. We found a direct relationship\nbetween the degree of FAs unsaturation and toxicity of Aβ1–42\nfibrils formed in their presence. Specifically, with an increase in\nthe degree of unsaturation, the toxicity A<sub>β1–42</sub>/FA fibrils increased. These results indicate that fully saturated\nor monounsaturated FAs could be used to decrease the toxicity of amyloid\naggregates and, consequently, decelerate the development of AD.